Cytogenetic evaluation of telomere dysfunction: Chromosomal aberrations involving telomeres and interstitial telomeric sequences

BOLZÁN, A,D,

Telomeres: Function, Shortening and Lengthening

Nova Science Publishers

Lugar: New York; Año: 2009; p. 133 - 185

Telomeres are specialized nucleoproteic complexes localized at the physical ends of linear eukaryotic chromosomes that maintain their stability and integrity, protecting chromosome ends from degradation and allowing them to be distinguished from deleterious DNA double-strand breaks (DSB), thus preventing chromosome end fusion. Therefore, telomere function is essential for continuous cellular proliferation and chromosomal stability maintenance. Dysfunctional telomeres can promote chromosome instability -through the so-called breakage-fusion-bridge (BFB) cycles, leading to DNA amplifications and terminal deletions-, cell cycle arrest and cell death. In all vertebrates, the DNA component of telomeres is constituted by (TTAGGG)n repeats and can be localized at the terminal regions of chromosomes (i.e., true telomeres) or at intrachromosomal sites (the so-called interstitial telomeric sequences or ITS, located close to the centromeres or between the centromere and the telomere). Telomere dysfunction can be evaluated at the cytogenetic level by identifying and analyzing the chromosomal aberrations involving telomeres and ITS. To this end, different techniques, including conventional Fluorescence in situ hybridization (FISH), Primed in situ labeling (PRINS), and Chromosome Orientation FISH (CO-FISH) with a (pan)telomeric (i.e., which identifies simultaneously all of the telomeres in a metaphase cell) DNA or Peptide Nucleic Acid (PNA) probe can be applied. In this review, we will consider each of these aberrations in detail, their mechanism of origin and their significance for telomere biology studies in vertebrate species.